The Department of Human Genetics at the University of Chicago is highly dependent on automated DNA sequencing for its research. Large- scale sequencing is used in the detection of disease-causing mutations, complex trait mapping, population surveys of DNA polymorphism, and studies of human and primate evolution. Presently, all the above studies rely on a single ABI-377 DNA sequencer in our Department's sequencing facility. This machine, already overtaxed by current demands, is projected to meet only one-third of researcher demand two years from now. To forestall the looming crisis, we propose to acquire an ABI-3700 DNA sequencer. The capacity of this machine is more than double that of ABI-377. Together, the two machines will be able to process over 150,000 sample per year, a volume that should meet our sequencing and genotyping needs in the coming years. Additionally, ABI-3700 has a number of features (e.g. automated sample loading and highly sensitive signal detection), which allow easier operation and better results. In sum, the Department of Human Genetics has a pressing scientific need for the ABI-3700 sequencer. It also has the management structure and technical expertise to operate it effectively. Finally, the Department has a strong financial commitment to support the long-term performance of its sequencing facility. Minerals play key roles in numerous biological reactions within the body and adequate intakes are essential to maintain optimum health. Despite the key role of minerals in human physiology, numerous questions exist on the ability of individuals to modify mineral metabolism during periods of increased nutrient demand, mineral deficiency or disease. Early human studies of mineral metabolism relied on the use of mineral radioisotopes. These studies are no longer ethical in all population groups and the difficulties and costs associated with disposal of radiotracers have shifted human studies to alternate methodological approaches. The current state-of-the-art method utilized to study mineral kinetics in vivo involves administration of oral and intravenous stable mineral isotopes and analysis of these isotopes using mineral isotope ratio mass spectrometry. At present, the majority of facilities in the United States with the instrumentation required for these analyses are devoted to geological or nuclear applications. We currently are one of the few facilities using this instrumentation for biological applications and have a Finnigan THQ thermal ionization mass spectrometer. Using our existing instrumentation, we have been very successful in applying mineral isotope techniques in human studies and have assembled a critical mass of NIH funded investigators that rely heavily on the current instrumentation for successful completion of their research. However, the limited sample capacity of the existing instrumentation and scarcity of these mass spectrometers has substantially restricted the application of these techniques to issues of relevance to human health. This proposal requests funds to purchase a Finnigan Element 2 high-resolution magnetic sector inductively coupled plasma mass spectrometer. Acquisition of this instrument will substantially improve sample throughput, precision and sensitivity compared to existing instrumentation and will enable the major user group at Johns Hopkins University, the USDA, NASA, Yale, Nemours Children's Clinic and the Mayo Clinic to continue their work in numerous federally funded projects addressing both basic and clinical research on mineral metabolism in healthy and diseased human populations.